Inorganic pyrophosphate (PPi) is produced in living cells in numerous metabolic pathways. These include the synthesis of polymers such as DNA, RNA, protein, and polysaccharides as well as small molecules such as cyclic-GMP and cyclic-AMP. PPi is also produced by oxidative phosphorylation and glycolysis. Most of these reactions are readily reversible in the presence of excess PPi, and PPi, itself, inhibits some of the cellular enzymes involved in these metabolic pathways. In order to promote the forward reactions and stabilize the reaction products, it is essential that PPi be removed. The enzyme pyrophosphatase (PPase) makes this energetically favorable hydrolysis of PPi possible.
PPase has been studied extensively in yeast and bacteria. Its activity has been shown to be essential for cell viability, and it may be essential for the fidelity of DNA replication as well. PPase is widely distributed in mammalian tissues where its activity varies widely. Little is known about how PPase activity is regulated in mammals or about the functions of PPase isolated from specific tissues. Multiple isoforms of PPase have, however, been found in humans and a number of other animals, perhaps indicating that there are functionally distinct isoforms of the enzyme in mammals. Bovine retina contains the highest level of PPase activity found in any mammalian tissue, and this enzyme has been sequenced and characterized (Yang, Z and Wensel, T G (1992) J Biol Chem 267: 24634-40, 24641-7). PPase activity was found to be essential for controlling PPi levels and the synthesis and degradation of cGMP which, in turn, controls the process of phototransduction in these cells.
The discovery of polynucleotides encoding pyrophosphatase, and the molecules themselves, presents the opportunity to investigate the role of pyrophosphatase in controlling the various metabolic pathways in cells involving PPi synthesis. The discovery of new pyrophosphatase molecules satisfies a need in the art by providing new diagnostic or therapeutic compositions useful in the treatment of diseases and conditions associated with uncontrolled cell signaling and cell proliferation such as inflammatory diseases and cancer.